Although we believe that the thyrotropin-releasing hormone (TRH) is also prolactin-releasing hormone (PRH), in monkeys and man, we will attempt to isolate PRH separate from TRH from the hypothalami of pigs. Others have reported that a partially purified preparation from pig and rat hypothalami free of TRH releases PRL in vivo in rats. Studies also will be performed to isolate prolactin-inhibiting hormone (PIF), growth hormone-releasing hormone (GH-RH), and growth inhibiting hormone (GIF), from porcine hypothalami, to determine their chemical structures, and to prepare them by organic chemical synthesis. The identity of the natural and synthetic hormones will be determined chemically and by studying their biological activities in vivo and in vitro in mice, rats, and monkeys. Since there is now good evidence that the effects of T3, estrogen, PIF and TRH are interrelated in determining the amount of PRL release, these interrelationships will be studied. Also planned are limited physiological, activity-structure, and mechanism of action studies of these hormones as well as clinical TRH studies in men and women with thyroid disorders. Once the activity and safety of the hypothalamic inhibiting and releasing hormones have been established in rats and monkeys their effects will be determined in man.